Myocardial Expression of a Dominant-Negative Form of Daxx Decreases Infarct Size and Attenuates Apoptosis in an In Vivo Mouse Model of Ischemia/Reperfusion Injury

Roubille, François; Combes, Stéphane; Leal-Sanchez, Juani; Barrère, Christian; Cransac, F.; Sportouch, Catherine; Gahide, G.; Serre, Isabelle; Kupfer, Elodie; Richard, Sylvain; Hueber, Anne-Odile; Nargeot, Joël; Piot, Christophe; Barrère-Lemaire, Stéphanie

doi:10.1161/circulationaha.107.694844

Cited by 36 publications

(32 citation statements)

References 48 publications

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“…Nuclear localization of Daxx was unaffected by BSO. The role of Daxx in cell death and its action following translocation has been a matter of debate (22,40,49,51). However, results presented herein demonstrate that translocation of Daxx to cytosol from the nucleus occurs only when nuclear DJ-1 levels decrease.…”

Section: Discussionmentioning

confidence: 99%

DJ-1 Loss by Glutaredoxin but Not Glutathione Depletion Triggers Daxx Translocation and Cell Death

Saeed

Ray

Valli

et al. 2010

Antioxidants & Redox Signaling

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Environmental and genetic causes are implicated in the etiopathogenesis of Parkinson's disease (PD), a neurodegenerative movement disorder. DJ-1, a putative gene recessively linked to early onset PD, functions as an antioxidant, transcriptional co-activator, and molecular chaperone. We examined DJ-1 status following global perturbation of protein thiol homeostasis by depleting cellular antioxidant glutathione or downregulating glutaredoxin 1, a thiol disulfide oxidoreductase, wherein both paradigms generate oxidative stress. While these perturbations did not affect expression of DJ-1 mRNA, downregulation of glutaredoxin 1 but not glutathione depletion caused loss of DJ-1 protein, translocation of Daxx (a death-associated protein) from nucleus, and cell death. Overexpression of wild-type DJ-1, but not the cysteine mutants, prevented Daxx translocation and cytotoxicity. Protease inhibitors prevented constitutive DJ-1 loss. Residual DJ-1 was present in reduced state, indicating that DJ-1 when oxidized was degraded through proteolysis. Thus, loss of DJ-1 occurring through its oxidative modification and subsequent proteolysis mediated through dysregulation of thiol disulfide oxidoreductase may contribute to pathogenesis of sporadic PD, thus providing a link between environmental challenges and constitutive levels of this vital protein.

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Section: Discussionmentioning

confidence: 99%

DJ-1 Loss by Glutaredoxin but Not Glutathione Depletion Triggers Daxx Translocation and Cell Death

Saeed

Ray

Valli

et al. 2010

Antioxidants & Redox Signaling

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“…Furthermore, many of the mechanistic targets of DJ-1 as an antioxidant are also related to these disease entities. For example, Daxx promotes prostate cancer tumorigenicity via suppression of autophagy (Puto et al, 2015), exhibits cytoplasmic translocation in substantia nigra pars compacta in a mouse model of PD (Karunakaran et al, 2007), and increases infarct size and potentiates apoptosis in a mouse model of cardiac ischemia/reperfusion injury (Roubille et al, 2007). Activation of Nrf2 pathway is beneficial against lung squamous cell carcinoma (Cescon et al, 2015), reduces protein aggregation, neuronal death and inflammation in early-stage PD (Lastres-Becker et al, 2012), and potentiates cell survival after ischemic myocardial ischemia reperfusion injury (Gurusamy et al, 2007).…”

Section: Activation Of Endogenous Dj-1 As a Common Therapeutic Targetmentioning

confidence: 99%

Activation of endogenous antioxidants as a common therapeutic strategy against cancer, neurodegeneration and cardiovascular diseases: A lesson learnt from DJ-1

Chan

2015

Pharmacology & Therapeutics

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“…9 Male mice (22 to 30 g) were anesthetized with an intramuscular injection of an anesthetic mixture comprising ketamine (50 mg/kg; Imalgène 500, Merial, France), xylazine (10 mg/kg; Rompun 2%, Bayer, France), and chlorpromazine (1.25 mg/kg; Largactil 5 mg/mL, Sanofi-aventis, France). Mice were ventilated via a tracheal intubation on a Harvard rodent respirator (tidal volume, 7.2 L/g body mass; respiratory rate, 200 breaths per min).…”

Section: Surgical Preparationmentioning

confidence: 99%

Delayed Postconditioning in the Mouse Heart In Vivo

Roubille¹,

Franck-Miclo²,

Covinhes³

et al. 2011

Circulation

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Background-Reperfusion during acute myocardial infarction remains the best treatment for reducing infarct size.Postconditioning, applied at the onset of reperfusion, reduces myocardial infarction both in animals and humans. The objective of this study was to identify the time delay to apply postconditioning at reperfusion, allowing preservation of cardioprotection in the mouse myocardium. This is a major issue in the management of acute myocardial infarction patients. Methods and Results-Mice were subjected to 40 minutes of ischemia and 60 minutes of reperfusion (IR 60Ј ).Postconditioning protocols corresponding to repetitive ischemia (3 cycles of 1 minute of ischemia and 1 minute of reperfusion) were applied during early reperfusion at various time durations (⌬t) after reopening of the coronary artery (⌬tϭ10 seconds, 1,5,10,15,20, 30, and 45 minutes; PostC ⌬t ). Infarct size/area at risk was reduced by 71% in PostC ⌬1 compared with IR 60Ј mice (Pϭ5ϫ10 Ϫ6 ). There was a linear correlation (r 2 ϭ0.91) between infarct size and ⌬t, indicating that the cardioprotective effect of delayed postconditioning was progressively attenuated when ⌬t time increased. The protective effect of PostC ⌬1 and PostC ⌬15 was still effective when the duration of reperfusion was prolonged to 24 hours (IR 24 hours ; PostC ⌬1 and PostC ⌬15 versus IR 24 hours , Pϭ0.001). Similar results were obtained for internucleosomal DNA fragmentation and lactate dehydrogenase release. Key Words: apoptosis Ⅲ ischemia Ⅲ myocardial infarction Ⅲ postconditioning Ⅲ reperfusion injury A cute myocardial infarction is a major cause of heart failure and death. Rapid reperfusion of the ischemic myocardium, by either thrombolysis or primary percutaneous coronary intervention, remains the best treatment for attenuating myocardial infarction. However, reperfusion itself has the potential to initiate additional lethal injury. This deleterious phenomenon culminates in death of cardiac cells that were viable immediately before myocardial reperfusion. 1 New strategies that directly target the reperfusion phase could improve clinical outcomes of acute myocardial infarction. [2][3][4] One such strategy, first described by Zhao and colleagues, 5 is called postconditioning. Applying intermittent episodes of myocardial ischemia/reperfusion at the early moments of reperfusion reduces myocardial infarction in every animal species tested, including mice. 6 Similar beneficial effects were recently demonstrated in patients who underwent primary percutaneous coronary intervention for acute coronary occlusion. 3,4 Conclusions-This Editorial see p 1315 Clinical Perspective on p 1336There appears to be a consensus that the delay after which the first reocclusion is established can only be short, but the available data are surprisingly sparse. 7 In a rat model, the beneficial effect of postconditioning was reported as lost when the delay between reperfusion and the first reocclusion was shifted from 10 to 60 seconds. 8 Since then, postconditioning maneuvers were initiated within 1 ...

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Myocardial Expression of a Dominant-Negative Form of Daxx Decreases Infarct Size and Attenuates Apoptosis in an In Vivo Mouse Model of Ischemia/Reperfusion Injury

Cited by 36 publications

References 48 publications

DJ-1 Loss by Glutaredoxin but Not Glutathione Depletion Triggers Daxx Translocation and Cell Death

DJ-1 Loss by Glutaredoxin but Not Glutathione Depletion Triggers Daxx Translocation and Cell Death

Activation of endogenous antioxidants as a common therapeutic strategy against cancer, neurodegeneration and cardiovascular diseases: A lesson learnt from DJ-1

Delayed Postconditioning in the Mouse Heart In Vivo

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